Although the occurrence of estrogen receptor (ER) has been used to classify breast carcinomas, the association between expression of ER and the molecular basis of tumor biology remains poorly understood. The long- term objective of this research project is to identify genes which are coordinately regulated with the expression of ER. The estrogen receptor factor-1 (ERF-1) transcription factor has recently been identified which regulates expression of ER in breast carcinoma. It is anticipated that one or a number of genes which are coordinately expressed with ER will also be regulated by ERF-1. By using techniques of differential screening and differential display, genes will be isolated which are consistently expressed or absent in ER- positive cell lines when compared to ER-negative cell lines. These cDNAs will be sequenced and compared to sequences in Genbank. These cDNAs will then be used as probes on Northern blots and primers for reverse transcriptase-polymerase chain reaction (RT-PCR) will be generated to examine expression in primary tumors. These studies will define differences in expression consistently found between ER-positive and ER- negative tumors. These results will expand our understanding of the basis for improved prognosis in patients with ER positive tumors.